Safety and Efficacy Study of Oral Ferric Iron To Treat Iron Deficiency Anaemia in Quiescent Ulcerative Colitis (AEGIS-1)

A Prospective, Multicentre, Randomised, Double-blind, Placebo Controlled Study With Oral ST10-021 for the Treatment of Iron Deficiency Anaemia in Subjects With Quiescent Ulcerative Colitis Where Oral Ferrous Preparations Have Failed or Cannot be Used (AEGIS 1)

The purpose of this study is to determine whether ST10-021, an oral ferric iron preparation, is safe and effective in the treatment of iron deficiency anaemia (IDA) in subjects with non-active ulcerative colitis (UC).

As no curative treatment is currently available for ulcerative colitis (UC), treatment options are restricted to controlling symptoms, maintaining remission and preventing relapse. As such, treatment of iron deficiency anaemia (IDA), a key symptom of the disease, is integral to the medical management of UC. Iron deficiency anaemia in UC is a chronically debilitating disorder which has a significant impact on the quality of life of affected subjects. Characteristic symptoms of IDA include chronic fatigue, headache, and subtle impairment of cognitive function. Up to one third of subjects with UC suffer from recurrent anaemia, with hospitalization required in severe cases. First line standard therapy for mild to moderate IDA in UC is typically oral ferrous products (OFP), however this is often not successful. Many subjects are intolerant and suffer from continuously occurring side effects, occasional exacerbation of inflammatory lesions and failure to correct iron deficiency. Common adverse effects of OFP include nausea, epigastric discomfort and constipation, all of which are dose-related and appear especially evident in subjects with UC.

As compared to oral ferrous iron, oral ferric iron can be administered with improved tolerability and the total dose exposure of unabsorbed iron within the gastrointestinal tract is significantly reduced. In addition, the iron is retained in its chelated form if not absorbed and this may reduce the risk of irritation within the gastrointestinal tract. Clinical studies conducted to date provide preliminary evidence for the therapeutic potential of ST10-021 in patients with IDA in Inflammatory Bowel Disease, including UC.

The purpose of this study is to determine whether ST10-021 is safe and effective in the treatment of IDA in subjects with non-active UC. In an effort to target an underserved population, the study will include only those subjects who have failed OFP in the past, or where OFP cannot be used.

Inclusion Criteria:

• Competency to understand and sign the IEC/IRB approved informed consent form prior to any study mandated procedure, and willing/able to comply with study requirements
• Age ≥ 18 years
• Current diagnosis of quiescent UC as defined by SCCAI score of < 4
• Current diagnosis of IDA as defined by Hb ≥ 9.5 g/dl and <12.0 g/dl for women and ≥ 9.5 g/dl and <13.0 g/dl for men; ferritin < 30 µg/l
• Prior OFP failure as defined per protocol
• If receiving protocol-allowed immunosuppressant must be on stable dose
• Females of childbearing potential must agree to use a reliable method of contraception

Exclusion Criteria:

• Anaemia due to any cause other than iron deficiency
• Intramuscular or intravenous injection or administration of depot iron preparation, blood infusions, or erythropoietin within 3 months
• Oral iron supplementation use within 1 month
• Use of immunosuppressant with known effect of anaemia induction within 1 month
• Vitamin B12 or Folic Acid injection/infusion within 4 weeks
• Untreated Vitamin B-12 or Folic Acid deficiency
• Known hypersensitivity or allergy to ST10-021 or components of the study medication, or contraindication for treatment with iron preparations
• Other chronic or acute inflammatory or infectious diseases
• Creatinine > 2.0 mg/dl
• AST or ALT levels ≥ 5 times the upper limit of normal
• Cardiovascular, liver, renal, hematologic, gastrointestinal, immunologic, endocrine, metabolic, or central nervous system disease that may adversely affect the safety of the subject and/or efficacy of the study drug or severely limit the lifespan of the subject
• History of malignancy within the past 5 years (except in situ removal of basal cell carcinoma)
• Significant neurologic or psychiatric symptoms resulting in disorientation, memory impairment, or inability to report accurately that might interfere with treatment compliance, study conduct or interpretation of the results
• Participation in another interventional clinical study within 30 days or during the study
• Inmates of a psychiatric ward, prison, or other state institution
• Investigator or any other team member involved directly or indirectly in the conduct of the clinical study
• Scheduled or expected hospitalization and/or surgery during the course of the study
• Females who are pregnant or lactating